Immunotherapy offers an attractive approach to the control of cancer. Passive immunotherapy with specifically sensitized cells holds particular promise, but requires the ability to consistently develop large numbers of lymphoid cells capable of eliminating the tumor in vivo and an understanding of T cell functions and interactions. Newly developed methods for isolation, characterization, expansion, long-term growth and cloning of lymphoid cells in culture, make it possible to achieve these goals. Reliable experimental models are now required to test and refine this potentially very valuable mode of treatment and determine its applicability to naturally occurring, established cancers. In an unique model system developed in our laboratory, acute leukemia in mice undergoes predictable, immunologically-mediated, spontaneous regression. Normal T cell and macrophage functions are essential for regression to occur. In a consistent fraction of clinically regressed animals, the leukemia spontaneously recurs. Under support of this grant, we have shown that leukemia regression can be efficiently induced in progressor leukemia mice by transfer of in vitro cultured T cells that are specifically reactive to virus/leukemia cell antigens. This immunotherapy is effective even in fully leukemic animals and requires no concurrent or prior adjunctive treatment such as irradiation or cytotoxic drugs. Helper Lyt 1+ cells are implicated in causing permanent disease cures, while cytotoxic Lyt 2+ cells cause temporary leukemia remissions. The aims of the present study include: complete characterization of the effector cells, their antigenic specificity and mechanism of action in vivo; determination of the involvement of lymphokines in successful immunotherapy; and development and characterization of effective immunotherapeutic protocols for prevention and treatment of leukemic recurrence, the outstanding problem in cancer management.